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Fibroblast activation protein

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https://www.readbyqxmd.com/read/28646679/hypoxia-induced-adam-17-expression-is-mediated-by-rsk1-dependent-c-ebp%C3%AE-activation-in-human-lung-fibroblasts
#1
Jing-Yun Chen, Chien-Huang Lin, Bing-Chang Chen
Hypoxia was identified as a mediator of lung fibrosis in patients with chronic obstructive asthma (COA). Overexpression of a disintegrin and metalloproteinase 17 (ADAM 17) and connective tissue growth factor (CTGF) leads to development of tissue fibrosis. However, the signaling pathway in hypoxia-induced ADAM 17 expression remains poorly defined. In this study, we investigated the roles that ribosomal S-6 kinase 1 (RSK1)/CCAAT/enhancer-binding protein β (C/EBPβ)-dependent ADAM 17 expression plays in hypoxia-induced CTGF expression in human lung fibroblasts...
June 21, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28646304/ndrg2-knockdown-promotes-fibrosis-in-renal-tubular-epithelial-cells-through-tgf-%C3%AE-1-smad3-pathway
#2
Zhibo Jin, Chaohui Gu, Fengyan Tian, Zhankui Jia, Jinjian Yang
Renal fibrosis is a common pathological pathway of various chronic kidney diseases progressing to end-stage renal disease and is characterized by tubular atrophy, fibroblast/myofibroblast activation and excessive deposition of extracellular matrix (ECM). N-Myc downstream-regulated gene-2 (NDRG2) is reported to be associated with liver fibrosis in rats. However, the biological function of NDRG2 in renal fibrosis remains unclear. Therefore, we investigate the effect of NDRG2 on renal fibrosis and the underlying mechanism of NDRG2 in TGF-β1-induced renal tubular epithelial cells (HK-2)...
June 23, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28645635/cytotoxicity-of-the-coagulant-moringa-oleifera-lectin-cmol-to-b16-f10-melanoma-cells
#3
Luciana de Andrade Luz, Franco Aparecido Rossato, Rute Alves Pereira E Costa, Thiago Henrique Napoleão, Patrícia Maria Guedes Paiva, Luana Cassandra Breitenbach Barroso Coelho
Moringa oleifera seeds are used in alternative medicine to treat inflammation, tumors and bacterial and protozoan infections, for example. The seeds contain lectins, which are carbohydrate-binding proteins with several biological properties including cytotoxicity to cancer cells. In this work, we examined the cytotoxicity of the coagulant M. oleifera lectin (cMoL) on B16-F10 murine melanoma cells. cMoL cytotoxic effects were evaluated through trypan blue assay and flow cytometry analysis. Mitochondrial superoxide levels and activation of caspases 3, 8 and 9 were measured...
June 20, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28644986/designing-novel-inhibitors-against-histone-acetyltransferase-hat-%C3%A2-gcn5-of-plasmodium-falciparum
#4
Amarjeet Kumar, Krishanu Bhowmick, Kunwar Somesh Vikramdeo, Neelima Mondal, Naidu Subbarao, Suman Kumar Dhar
During active proliferation phase of intra-erythrocytic cycle, the genome of P. falciparum is regulated epigenetically and evolutionary conserved parasite-specific histone proteins are extensively acetylated. The reversible process of lysine acetylation, causing transcriptional activation and its deacetylation, causing transcriptional repression is regulated by balanced activities of HATs and HDACs. They are also known to regulate antigenic variations and gametocytic conversion in P. falciparum. These histone modifying enzymes have been identified as potential targets for development of anitmalarials in literature...
June 10, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28643937/proinflammatory-effects-and-mechanisms-of-calprotectin-on-human-gingival-fibroblasts
#5
H Gao, J Hou, H Meng, X Zhang, Y Zheng, L Peng
BACKGROUND AND OBJECTIVE: Calprotectin (S100A8/A9) is a heterodimer of S100A8 and S100A9 and is associated with multiple inflammatory diseases, including Crohn's disease, rheumatoid arthritis and periodontitis. Levels of calprotectin are elevated in the gingival crevicular fluid of patients with periodontitis; however, the effects of calprotectin on human gingival fibroblasts (HGFs) remain unknown. This study investigated the proinflammatory activity of calprotectin on HGFs and the functional receptors and signaling pathways engaged by calprotectin...
June 23, 2017: Journal of Periodontal Research
https://www.readbyqxmd.com/read/28642261/transforming-growth-factor-beta-stimulates-smad1-5-signaling-in-pulmonary-artery-smooth-muscle-cells-and-fibroblasts-of-the-newborn-mouse-through-alk1
#6
Huili Zhang, Lili Du, Ying Zhong, Kathleen C Flanders, Jesse D Roberts
The intracellular signaling mechanisms through which TGFβ regulates pulmonary development are incompletely understood. Canonical TGFβ signaling involves Smad2/3 phosphorylation, Smad2/3·Smad4 complex formation and nuclear localization, and gene regulation. Here we show that physiologically relevant TGFβ1 levels also stimulate Smad1/5 phosphorylation, typically a mediator of bone morphogenetic protein (BMP) signaling, in mouse pup pulmonary artery smooth muscle cells (mPASMC) and lung fibroblasts and other interstitial lung cell lines...
June 22, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28642198/treatment-of-intestinal-fibrosis-in-experimental-inflammatory-bowel-disease-by-the-pleiotropic-actions-of-a-local-rho-kinase-inhibitor
#7
Tom Holvoet, Sarah Devriese, Karolien Castermans, Sandro Boland, Dirk Leysen, Yves-Paul Vandewynckel, Lindsey Devisscher, Lien Van den Bossche, Sophie Van Welden, Melissa Dullaers, Roosmarijn E Vandenbroucke, Riet De Rycke, Karel Geboes, Arnaud Bourin, Olivier Defert, Pieter Hindryckx, Martine De Vos, Debby Laukens
BACKGROUND: Intestinal fibrosis resulting in (sub)obstruction is a common complication of Crohn's disease (CD). Rho kinases (ROCKs) play multiple roles in TGFβ1-induced myofibroblast activation that could be therapeutic targets. Because systemic ROCK inhibition causes cardiovascular side-effects, we evaluated the effects of a locally acting ROCK inhibitor (AMA0825) on intestinal fibrosis. METHODS: Fibrosis was assessed in mouse models using dextran sulfate sodium and adoptive T cell transfer...
June 19, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28642129/fucoxanthin-inhibits-profibrotic-protein-expression-in-vitro-and-attenuates-bleomycin-induced-lung-fibrosis-in-vivo
#8
Sun Young Ma, Won Sun Park, Dae-Sung Lee, Grace Choi, Mi-Jin Yim, Jeong Min Lee, Won-Kyo Jung, Sae Gwang Park, Su-Kil Seo, Sung Jae Park, Il Yong Han, Yung Hyun Choi, Il-Whan Choi
Pulmonary fibrosis, a potentially fatal disease, results from acute and chronic interstitial lung diseases. Fucoxanthin (Fx), a carotenoid found in brown seaweed, shows a wide range of pharmacological activities. In this study, we investigated the antifibrotic effects of fucoxanthin and their underlying molecular mechanisms in transforming growth factor-beta1 (TGF-β1)-stimulated human pulmonary fibroblasts (HPFs). Thus, the effects of Fx on TGF-β1-induced expression of fibrotic factors, such as alpha-smooth muscle actin (α-SMA), type 1 collagen, fibronectin, and interleukin-6 (IL-6), in HPFs were investigated...
June 19, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28640945/production-of-human-vitronectin-in-nicotiana-benthamiana-using-the-inpact-hyper-expression-platform
#9
Benjamin Dugdale, Maiko Kato, Pradeep Deo, Manuel Plan, Mark Harrison, Robyn Lloyd, Terry Walsh, Robert Harding, James Dale
Human vitronectin (hVN) is a glycoprotein that functions as a cell adhesion molecule and a regulator of coagulation in blood plasma and the extracellular matrix. In vitro, hVN is added to serum-free media in order to promote the adhesion of animal cells to tissue culture surfaces and the proliferation of undifferentiated stem cells. Here, we report the production of hVN in Nicotiana benthamiana using the inducible In Plant Activation (INPACT) hyper-expression platform. N. benthamiana plants were transformed with an INPACT expression cassette encoding hVN, and both the Tobacco yellow dwarf virus Rep/RepA activator and Tomato bushy stunt virus p19 gene under the transcriptional control of the ethanol-inducible AlcR:alcA gene switch...
June 22, 2017: Plant Biotechnology Journal
https://www.readbyqxmd.com/read/28640441/adipose-tissue-derived-omentin-1-function-and-regulation
#10
Takuya Watanabe, Kaho Watanabe-Kominato, Yui Takahashi, Miho Kojima, Rena Watanabe
Omentin-1, also known as intelectin-1, is a recently identified novel adipocytokine of 313 amino acids, which is expressed in visceral (omental and epicardial) fat as well as mesothelial cells, vascular cells, airway goblet cells, small intestine, colon, ovary, and plasma. The level of omentin-1 expression in (pre)adipocytes is decreased by glucose/insulin and stimulated by fibroblast growth factor-21 and dexamethasone. Several lines of experimental evidence have shown that omentin-1 plays crucial roles in the maintenance of body metabolism and insulin sensitivity, and has anti-inflammatory, anti-atherosclerotic, and cardiovascular protective effects via AMP-activated protein kinase/Akt/nuclear factor-κB/mitogen-activated protein kinase (ERK, JNK, and p38) signaling...
June 18, 2017: Comprehensive Physiology
https://www.readbyqxmd.com/read/28639899/tweak-fn14-signaling-in-tumors
#11
Guanglei Hu, Weihui Zeng, Yumin Xia
TWEAK (tumor necrosis factor-related weak inducer of apoptosis), a member of the tumor necrosis factor superfamily, acts on cells by binding to its only receptor named Fn14 (fibroblast growth factor-inducible 14). Their engagement activates a number of intracellular signal transduction cascades and consequently leads to cell death, proliferation, migration, or survival depending on the cellular contexts. Studies have indicated that the expression of TWEAK and Fn14 is upregulated in many solid tumors compared with healthy tissues...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28638064/quantitative-phosphoproteomics-reveals-a-role-for-collapsin-response-mediator-protein-2-in-pdgf-induced-cell-migration
#12
Adil R Sarhan, Justyna Szyroka, Shabana Begum, Michael G Tomlinson, Neil A Hotchin, John K Heath, Debbie L Cunningham
The Platelet Derived Growth Factor (PDGF) family of ligands have well established functions in the induction of cell proliferation and migration during development, tissue homeostasis and interactions between tumours and stroma. However, the mechanisms by which these actions are executed are incompletely understood. Here we report a differential phosphoproteomics study, using a SILAC approach, of PDGF-stimulated mouse embryonic fibroblasts (MEFs). 116 phospho-sites were identified as up-regulated and 45 down-regulated in response to PDGF stimulation...
June 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28635952/yunis-var%C3%A3-n-syndrome-caused-by-biallelic-vac14-mutations
#13
Matthew A Lines, Yoko Ito, Kristin D Kernohan, Wendy Mears, Julie Hurteau-Miller, Sunita Venkateswaran, Leanne Ward, Karine Khatchadourian, Jeff McClintock, Priya Bhola, Philippe M Campeau, Kym M Boycott, Jean Michaud, André Bp van Kuilenburg, Sacha Ferdinandusse, David A Dyment
Yunis-Varón syndrome (YVS) is an autosomal recessive disorder comprising skeletal anomalies, dysmorphism, global developmental delay and intracytoplasmic vacuolation in brain and other tissues. All hitherto-reported pathogenic variants affect FIG4, a lipid phosphatase involved in phosphatidylinositol (3,5)-bisphosphate [PtdIns(3,5)P2] metabolism. FIG4 interacts with PIKfyve, a lipid kinase, via the adapter protein VAC14; all subunits of the resulting complex are essential for PtdIns(3,5)P2 synthesis in the endolysosomal membrane compartment...
June 21, 2017: European Journal of Human Genetics: EJHG
https://www.readbyqxmd.com/read/28632033/overexpression-of-alk5-induces-human-tenon-s-capsule-fibroblasts-transdifferentiation-and-fibrosis-in-vitro
#14
Shu-Hao Fu, Hui-Ying Wang, Jia-Ying Zhang, Hui-Min Shi, Nan Zhang, Wen Ye, Yi-Qin Xiao
PURPOSE: To investigate the involvement of activin receptor-like kinase 5 (ALK5) in human Tenon's capsule fibroblasts (HTFs) transdifferentiation and fibrosis. METHODS: (1) Cultured HTFs were treated with transforming growth factor beta 1 (TGF-β1) at different concentrations for different durations, mRNA expression of ALK5 and plasminogen activator inhibitor-1 (PAI-1) was measured by quantitative polymerase chain reaction (PCR) while protein expression of ALK5, α-smooth muscle actin (α-SMA), and extracellular matrix deposition including fibronectin (FN) and collagen I (Col1) was assessed by western blot...
February 28, 2017: Current Eye Research
https://www.readbyqxmd.com/read/28631941/analytical-characterization-of-methyl-%C3%AE-cyclodextrin-for-pharmacological-activity-to-reduce-lysosomal-cholesterol-accumulation-in-niemann-pick-disease-type-c1-cells
#15
Rong Li, Jon Hao, Hideji Fujiwara, Miao Xu, Shu Yang, Sheng Dai, Yan Long, Manju Swaroop, Changhui Li, Mylinh Vu, Juan J Marugan, Daniel S Ory, Wei Zheng
Methyl-β-cyclodextrin (MβCD) reduces lysosomal cholesterol accumulation in Niemann-Pick disease type C1 (NPC1) patient fibroblasts. However, the pharmacological activity of MβCD reported by different laboratories varies. To determine the potential causes of this variation, we analyzed the mass spectrum characteristics, pharmacological activity of three preparations of MβCDs, and the protein expression profiles of NPC1 patient fibroblasts after treatment with different sources of MβCDs. Our data revealed varied mass spectrum profiles and pharmacological activities on the reduction of lysosomal cholesterol accumulation in NPC1 fibroblasts for these three preparations of MβCDs obtained from different batches and different sources...
May 2017: Assay and Drug Development Technologies
https://www.readbyqxmd.com/read/28631426/hsp90%C3%AE-regulates-atm-and-nbn-functions-in-sensing-and-repair-of-dna-double-strand-breaks
#16
Rosa Pennisi, Antonio Antoccia, Stefano Leone, Paolo Ascenzi, Alessandra di Masi
The molecular chaperone heat shock protein 90 (Hsp90α) regulates cells proteostasis and mitigates the harmful effects of endogenous and exogenous stressors on the proteome. Indeed, the inhibition of Hsp90α ATPase activity affects the cellular response to ionizing radiation (IR). Although the interplay between Hsp90α and several DNA damage response (DDR) proteins has been reported, its role in the DDR is still unclear. Here, we show that ATM and NBN, but not 53BP1, RAD50, and MRE11, are Hsp90α clients as the Hsp90α inhibitor 17-(allylamino)-17-demethoxygeldanamycin (17-AAG) induces ATM and NBN polyubiquitination and proteosomal degradation in normal fibroblasts and lymphoblastoid cells lines...
June 20, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28630215/mechanisms-of-primary-drug-resistance-in-fgfr1-amplified-lung-cancer
#17
Florian Malchers, Meryem Seda Ercanoglu, Daniel Schütte, Roberta Castiglione, Verena Tischler, Sebastian Michels, Ilona Dahmen, Johannes Brägelmann, Roopika Menon, Johannes M Heuckmann, Julie George, Sascha Ansén, Martin L Sos, Alex Soltermann, Martin Peifer, Jurgen Wolf, Reinhard Büttner, Roman K Thomas
<br />The 8p12-p11 locus is frequently amplified in squamous cell lung cancer (SQLC); the receptor tyrosine kinase fibroblast growth factor receptor 1 (FGFR1) being one of the most prominent targets of this amplification. Thus, small molecules inhibiting FGFRs have been employed to treat FGFR1-amplified SQLC. However, only about 11% of such FGFR1-amplified tumors respond to single agent FGFR inhibition and several tumors exhibited insufficient tumor shrinkage, compatible with the existence of drug-resistant tumor cells...
June 19, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28629444/microrna-98-inhibits-the-cell-proliferation-of-human-hypertrophic-scar-fibroblasts-via-targeting-col1a1
#18
Sheng Bi, Linlin Chai, Xi Yuan, Chuan Cao, Shirong Li
BACKGROUND: Hypertrophic scarring (HS) is a severe disease, and results from unusual wound healing. Col1A1 could promote the hypertrophic scar formation, and the expression of Col1A1 in HS tissue was markedly higher than that in the normal. In present study, we aimed to identify miRNAs as post-transcriptional regulators of Col1A1 in HS. METHODS: MicroRNA-98 was selected as the key miRNA comprised in HS. The mRNA levels of miR-98 in HS tissues and the matched normal skin tissues were determined by qRT-PCR...
June 19, 2017: Biological Research
https://www.readbyqxmd.com/read/28629212/a-study-of-the-modulating-action-of-quercetin-on-biochemical-and-histological-alterations-induced-by-lead-exposure-in-the-liver-and-kidney-of-rats
#19
Azza Sedky, Hany Elsawy
Lead is a highly toxic metal and a very potent poison. Lead poisoning is a serious condition but can be treated. Quercetin is a flavonoid with many beneficial uses. The aim of the present study was to investigate the possible modulating action of quercetin as a model of an antioxidant against the toxic effects of lead acetate on liver and kidneys of rats. Rats were randomly divided into four groups: (i) saline group (control); (ii) lead group received i.p. lead acetate (20 mg/kg b.w.); (iii) quercetin group received i...
June 30, 2017: Chinese Journal of Physiology
https://www.readbyqxmd.com/read/28627680/bmp%C3%A2-7-suppresses-excessive-scar-formation-by-activating-the-bmp%C3%A2-7-smad1-5-8-signaling-pathway
#20
Jingdong Guo, Quan Lin, Ying Shao, Li Rong, Duo Zhang
Scarring is the inevitable consequence of wound repair, which may cause significant physical and mental pain to patients when excessive. Bone morphogenetic protein‑7 (BMP‑7) has been proved to inhibit TGF‑β‑induced fibrosis in various tissues including dermal papilla cells. However, the effect of BMP‑7 on hypertrophic scarring, a common proliferative disorder of dermal fibroblasts, has not been determined. To overcome this problem, the present study established a mouse model of thermal injury to investigate the inhibitory effects of BMP‑7 on scar formation...
June 14, 2017: Molecular Medicine Reports
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